Allylic and benzylic oxidation using cobalt(II) alkyl phosphonate modified silica

Article abstract of DOI:10.1016/S0040-4039(03)00833-5

The allylic and benzylic oxidation of a range of substrates proceeds in good yield using catalytic quantities of cobalt(II) alkyl phosphonate modified silica and tert-butyl hydroperoxide.

Full text of DOI:10.1016/S0040-4039(03)00833-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4283–4286
Allylic and benzylic oxidation using cobalt(II) alkyl phosphonate
modified silica
Magdalena Jurado-Gonzalez, Alice C. Sullivan* and John R. H. Wilson
Department of Chemistry, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
Received 18 February 2003; revised 17 March 2003; accepted 28 March 2003
Abstract—The allylic and benzylic oxidation of a range of substrates proceeds in good yield using catalytic quantities of cobalt(II)
alkyl phosphonate modified silica and tert-butyl hydroperoxide. © 2003 Elsevier Science Ltd. All rights reserved.
Allylic and benzylic oxidations are important transfor-
mations utilised in the preparation of a range of inter-
mediates and products for various chemical industries.
An example of the former is the oxidation of D5
steroids to their corresponding 5-en-7-one derivatives
and for the latter the benzylic oxidation of resorcinol to
terphthalic acid used in the production of poly(ethylene
terephthalate). A variety of chromium reagents have
been used for allylic oxidation. Examples include
chromium trioxide coupled with a number of bases
such as pyridine1 or 3,5-dimethylpyrazole.2 In addition
a number of chromate reagents have been utilised such
as pyridinium chlorochromate3 or dichromate4 as well
as sodium chromate.5 Invariably stoichiometric or
larger quantities have to be used to complete the oxida-
tion. As a consequence difficulties are usually encoun-
tered in working up these reactions and significant
quantities of environmentally hazardous chromium
residues have to be treated. Alternative oxidation tech-
nologies, preferably catalytic and heterogeneous, are
needed.
phase benzylic and allylic oxidation. A heterogeneous
cobalt(II) acetate tert-butyl hydroperoxide derived cat-
alyst has recently been reported for the allylic oxidation
of steroids.12
We recently reported13,14 the synthesis and characterisa-
tion of the first examples of phosphonate and phospho-
nic acid modified silicas 115 (Scheme 1). The silica ethyl
and propyl phosphonate materials, EPS and PPS, pre-
pared to date have Q:T ratios16,18 in the range 1:1 to
10:1. In all cases we found the T components to have
ca. 66% condensation and Q ca. 90%. Examples from
both the ethyl and propyl phosphonate modified silica
materials EPS3 and PPS2 with average formulae 2 and
3 were used in this study. Average formulae were
derived as previously described.13 Preparation of these
materials 2 and 3 utilised our earlier reported general
methodology.13 We have found that these phosphonic
acid modified silica materials can catalyse a wide range
of acid catalysed reactions.17
A number of metal derivatives of these ethyl and propyl
phosphonic acid modified silicas have been prepared18
and their chemistry and structural characteristics are
A variety of mainly homogeneous and a few heteroge-
neous catalytic methods for liquid phase allylic and
benzylic oxidation have been reported. Examples pri-
marily involve tert-butyl hydroperoxide along with cat-
alytic quantities of metal derivatives such as chromium
hexacarbonyl,6 chromium oxide,7 1,3-diol chromate
complexes,8 ruthenium trichloride,9 copper salts,10 man-
ganese(II) complexes11 or cobalt(II) acetate12 all of
which have been reported to effect homogeneous liquid
Keywords: benzylic; oxidation; steroids; cobalt; phosphonate; silica;
immobilised reagents.
* Corresponding author. Tel.: +44-207-882-3274; fax: +44-207-882-
7794; e-mail: a.c.sullivan@qmul.ac.uk
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00833-5

4284
M. Jurado-Gonzalez et al. / Tetrahedron Letters 44 (2003) 4283–4286
cobalt(II) immobilised on ethyl and propyl phospho-
nate modified silicas, CoEPS3 and CoPPS2 (Scheme 2).
As far as we are aware no cobalt(II) phosphonate based
homogeneous or heterogeneous reagent for liquid phase
catalytic allylic and benzylic oxidation has been
reported. Both the CoEPS3 and CoPPS2 materials were
prepared20 by treating the corresponding disodium sil-
ica phosphonates with an aqueous solution of cobalt(II)
acetate (Scheme 2). The filtered solid was washed exten-
sively with water and then with ether and finally dried
at 100°C and 0.01 torr. The cobalt(II) loading was
determined by atomic absorption following treatment
of the CoEPS3 and CoPPS2 materials with concen-
trated nitric acid to liberate the cobalt.
Scheme 2.
currently being investigated. We have reported19
recently the use of cerium(IV) immobilised on similar
alkyl phosphonate modified silica for the effective cata-
lytic oxidation of a wide range of alcohols with sodium
bromate as the re-oxidant. In this paper we wish to
report our initial work on the catalytic allylic and
benzylic oxidation of a variety of substrates utilising
Given the biological importance of steroid derivatives
we investigated the allylic oxidation of a number of
unsaturated derivatives 4–7. The results are shown in
Table 1.
Substratea
Product
Catalystb (mmol Co)
Time (h)
Temp. (°C)
Isolated yield (%)
4c
4c
4c
5
5
5
5
5
5
5
8
8
CoEPS3 (0.068)
CoPPS2 (0.096)
0d
20
20
24
24
24
24
24
24
24
24
1
55
70
70
50
50
50
50
50
50
50
50
50
50
50
50
61
80
0
9
9
9
9
9
9
9
9
CoEPS3 (0.068)
CoEPS3e (0.068)
CoEPS3e (0.068)
CoEPS3e (0.068)
CoEPS3 (0.058)
CoPPS2 (0.096)
CoPPS2e (0.096)
CoEPS3 (0.058)
0d
90
87
87
88
94
97
95
78f
0
5
5
6
6
24
24
24
48
10
10
11
CoPPS2 (0.096)
CoEPS3 (0.058)
CoPPS2 (0.096)
70
89
86
7
a All reactions were conducted in acetonitrile on a 1 mmol scale unless otherwise indicated.
b Co2+ concentration was determined by atomic absorption after the metal ion was liberated by treatment of the CoEPS3 or CoPPS2 with
concentrated nitric acid.
c Reaction conducted in benzene and 2 mmol of 4 was used.
d No CoEPS3 or CoPPS2 catalyst was used, 2 mmol of substrate and tert-butyl hydroperoxide in decane (12 mmol).
e Recycled catalyst; the catalyst was filtered, washed well with water and diethyl ether and then dried at 100°C and 0.01 torr.
f The standard test for catalyst leaching, was applied and no further conversion was observed in hot filtrates of the reaction mixture after a further
24 h.

M. Jurado-Gonzalez et al. / Tetrahedron Letters 44 (2003) 4283–4286
4285
Table 1. Apart from cholesterol acetate 4 where the
reaction was conducted in benzene, all other reactions
were performed in acetonitrile. Like the allylic oxida-
tions using the homogeneous metal derivatives men-
tioned above we used an excess of tert-butyl
hydroperoxide as the re-oxidant. In the absence of the
cobalt(II) catalysts, CoEPS3 and CoPPS2, no oxidation
was observed.
both the reaction conditions and the CoEPS and
CoPPS catalyst systems is currently being investigated
for both allylic and benzylic oxidations.
In conclusion we have demonstrated that cobalt(II)
alkyl phosphonate modified silica can effectively
catalyse the allylic and benzylic oxidation of a range of
substrates in very good yield without any apparent
leaching of the metal.
Oxidation of a variety of steroids 4–7 using either of the
catalysts, CoEPS3 or CoPPS2, gave the desired 5-en-7-
ones 8–11 in good isolated yields. A typical procedure21
involves stirring a mixture containing the catalyst at
concentrations of 3.4–9.66 mol% Co(II) and tert-butyl
hydroperoxide as the re-oxidant in a suitable solvent at
a temperature between 50 and 70°C. Although the
reaction is virtually complete within a couple of hours
the mixtures were routinely left to run overnight. Both
catalysts, CoEPS3 and CoPPS2, can be effectively recy-
cled as the examples with 5 demonstrate, giving similar
yields of 9 within experimental error. To check for
leaching, the catalyst was filtered, at the reaction tem-
perature, from the oxidation of 5 after one hour and
the filtrate was allowed to react for a further twenty
four hours. No further oxidation was observed. This
suggests that oxidation is occurring at the immobilised
cobalt(II). Using a similar procedure these CoEPS3 and
CoPPS2 catalysts can be used to oxidise a range of
other olefins to their corresponding enones (Table 2).
Examples of benzylic oxidation are also given in Table
2. In the examples explored to date no significant
difference in reactivity between the CoEPS3 and the
CoPPS2 catalysts has been noted. The optimisation of
Acknowledgements
We thank the EPSRC GR/M78281 for supporting this
work.
References
1. Dauben, G. W.; Lorber, M.; Fullerton, D. S. J. Org.
Chem. 1969, 34, 3587–3592.
2. Salmond, W. G.; Barta, M. A.; Havens, J. L. J. Org.
Chem. 1978, 43, 2057–2059.
3. Parish, E. J.; Chitrakorn, S.; Wei, T. Synth. Commun.
1986, 16, 1371–1375.
4. Parish, E. J.; Wei, T. Y. Synth. Commun. 1987, 17,
1227–1233.
5. Marshall, C. W.; Ray, R. E.; Laos, I.; Reigel, B. J. Am.
Chem. Soc. 1957, 79, 6308–6313.
6. Pearson, A. J.; Chen, Y.; Hsu, S.; Ray, T. Tetrahedron
Lett. 1984, 25, 1235–1238.
7. Muzart, J. Tetrahedron Lett. 1987, 28, 4665–4668.
8. Muzart, J. Tetrahedron Lett. 1987, 28, 3139–3142.
Table 2.

4286
M. Jurado-Gonzalez et al. / Tetrahedron Letters 44 (2003) 4283–4286
9. Miller, R. A.; Li, W.; Humprey, G. R. Tetrahedron Lett.
1996, 37, 3429–3432.
10. Salvador, J. A. R.; Sa e Melo, M. L.; Campos Neves, A.
further 30 min and then filtered. The white solid,
Na2EPS3, was washed well with distilled water and then
with ethanol and ether and finally dried under reduced
pressure (120°C and 0.01 torr for 12 h). Cobalt(II) acetate
tetrahydrate (0.7 g) dissolved in distilled water (15 ml)
was added to Na2EPS3 (1.21 g) and the resultant mixture
was stirred for 1 h. The blue purple solid was filtered and
washed with distilled water (1.5 L) and then with ethanol
and ether and finally dried under reduced pressure, 120°C
and 0.01 torr for 12 h, to afford CoEPS (1.13 g).
S. Tetrahedron Lett. 1997, 38, 119–122.
11. Pan, J.; Chen, K. J. Mol. Cat. A 2001, 176, 19–22.
12. Salvador, J. A. R.; Clark, J. H. Chem. Commun. 2001,
33–34.
13. Aliev, A.; Li Ou, D.; Ormsby, B.; Sullivan, A. C. J.
Mater. Chem. 2000, 10, 2758–2764.
14. Jurado-Gonzalez, M.; Li Ou, D.; Ormsby, B.; Sullivan,
A. C.; Wilson, J. R. H. Chem. Commun. 2001, 67–68.
15. Idealised structure assuming 100% condensation.
16. Q-environment [SiOn/2(OR%)4−n] n=1–4; T-environment
[SiR(O)n/2(OR%)3−n] n=1–3.
21. Typical procedure: A mixture containing the substrate (1
mmol) dissolved in acetonitrile (6 ml), cobalt(II) alkyl
phosphonate silica catalyst (60 mg) and tert-butyl
hydroperoxide (6 mmol in decane) was heated and stirred
under an atmosphere of nitrogen at the temperature and
period of time indicated in Tables 1 and 2. On comple-
tion the catalyst was filtered and washed well with
dichloromethane. The combined filtrate was washed well
with an aqueous sodium sulphite solution (10%) and then
with water, dried and concentrated under reduced pres-
sure. Purification where necessary, to remove traces of
starting material, was by recrystallisation or by column
chromatography.
17. Unpublished results.
18. Jurado-Gonzalez, M.; Sullivan, A. C.; Wilson, J. R. H. J.
Mater. Chem. 2002, 12, 3605–3609.
19. Al-Haq, N.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron
Lett. 2003, 44, 769–771.
20. Preparation of CoEPS3: A mixture containing EPS318
(1.82 g) was stirred in distilled water (15 ml) for 15 min
and then sodium hydroxide (1 M, 9.5 ml) was added
dropwise over 30 min. The mixture was stirred for a